1 - Especialidade de Genética Médica, Área Departamental de Pediatria Médica, Hospital de Dona Estefânia, Centro Hospitalar de Lisboa Central, EPE
2 - Centro de Medicina Laboratorial Germano de Sousa
3 - Serviço de Anatomia Patológica, Instituto Português de Oncologia de Lisboa Francisco Gentil EPE
4 - Unidade de Fetopatologia, Serviço de Anatomia Patológica, Centro Hospitalar de Lisboa Ocidental EPE
5 - Unidade de Fetopatologia, Serviço de Anatomia Patológica, Centro Hospitalar de Lisboa Central EPE
6 - Centro de Diagnóstico Pré-Natal, Maternidade Alfredo da Costa, Centro Hospitalar de Lisboa Central EPE
- XIX Reunião da Sociedade Portuguesa de Genética Humana, 5 a 7/11/2015 (poster)
Introduction: Osteochondrodysplasias or skeletal dysplasias (SD) are a genetically heterogenous group of disorders that affect growth morphology of the chondro-osseous tissues. Many SD can be identified by ultrasound (US) evaluation prenatally, but differential diagnosis may be challenging due to the large number of SD and their phenotypical variability with overlapping features. The confirmation of diagnosis usually relies on molecular testing, postdelivery radiographic studies and autopsy, including histomorphic analysis of cartilage and bone.
Methods: We report and characterize three clinical cases of fetal SD as a paradigm of the difficulty in diagnosing SD by US.
Results: All cases had shortening of fetal femora and humeri (<5th centile or -2SD) and invasive prenatal testing. In cases 1 and 2, SD was identified in 1st trimester US and a microarray for SD (9 genes, 47 mutations) was normal, but pregnancy was terminated due to phenotypic severity. Case 3 was identified in the 2nd trimester and a female was born prematurely. In case 1, fetal phenotype and histological findings are suggestive of Achondrogenesis 1A; in case 2, the possible diagnosis is Thanatophoric Dysplasia; in case 3, neonatal clinical and radiographic phenotype and increased urinary levels of phosphoethanolamine point to Hypophosphatasia. In all cases, DNA was stored and sequencing of TRIP11, FGFR3 and ALPL genes respectively is still ongoing.
Discussion: The molecular confirmation of the suspected clinical diagnosis is important to improve postnatal management of fetuses with SD and accurately determine recurrence risk and enable at-risk couples to access prenatal or preimplantation genetic testing in future pregnancies. We hope to enlighten the role of the medical geneticist in the diagnosis of SD, integrating clinical, radiographic and histopathological findings and keeping in mind that multidisciplinary approach is the key factor in the diagnosis of these disorders during perinatal period.
Palavras-chave: Fetal Skeletal Dysplasias, Perinatal Diagnosis, Achondrogenesis 1A, Thanatophoric Dysplasia, Hypophosphatasia